Circulating Human Metabolites Resulting From TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Hypocholesterolemic Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons From an Original ex vivo Clinical Trial

Autor: Wauquier, Fabien, Langhi, Cédric, Boutin-Wittrant, Line, Otero, Yolanda, Le Joubioux, Florian, Maugard, Thierry, Roux, Véronique, Macian, Nicolas, Pickering, Gisele, Bargetto, Maxime, Cazaubiel, Murielle, Peltier, Sébastien, Sirvent, Pascal, Wittrant, Yohann
Přispěvatelé: Clinic'n'Cell SAS, Valbiotis R & D [Riom], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, Valbiotis R&D [Perigny], La Rochelle Université (ULR), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Circulation
Circulation, 146, 2022
ISSN: 0009-7322
1524-4539
Popis: Introduction: TOTUM-070 is a patented polyphenol-rich compound which has shown hypocholesterolemic properties in preclinical studies. However, clinically validated approaches and further investigations on the mode of action at cellular level especially in humans are required for optimized care management. In this study, we designed an ex-vivo clinical innovative approach considering the metabolites produced by the digestive tract following the ingestion of TOTUM-070 in humans.Methods: Human serum was collected in healthy subjects before and following acute intake of 5g of TOTUM-070. Availability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum enriched with metabolites deriving from TOTUM-070 absorption was further incubated with human hepatocytes, pretreated or not with palmitate (250 μM). In such lipotoxic environment, hepatocyte behavior was monitored to determine whether and how TOTUM-070 metabolites may improve cholesterol metabolism in human.Results: In the presence of the human metabolites from TOTUM-070, human hepatocytes were protected from an induced lipotoxic stress. No effect on cell toxicity was detected in the presence of enriched sera. Hepatocyte protection was characterized by (1) the inhibition of both triglycerides (-41%, p
Databáze: OpenAIRE